Alcohol and Digestive Cancers Across Europe: Time for Change 2 Alcohol and Digestive Cancers Time for Change

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Contents

Introduction 3 Alcohol and Digestive Cancers 6 Alcohol and European Culture 7 Alcohol Type and Associated Risk 8 Alcohol and Oesophageal Cancer 12 Alcohol and Liver Cancer 14 Alcohol and Pancreatic Cancer 16 Alcohol and Colorectal Cancer 18 Alcohol and Gastric Cancer 20 Alcohol and Digestive Cancers — Implications for the Public 22 Alcohol and Digestive Cancers — Implications for Primary Care Practitioners 24 Alcohol and Digestive Cancers — Implications for Policy Makers 26 Time for Change 28 References 30

This report has been produced by UEG with support from a number of leading gastroenterology experts from across Europe, together with the European Association for the Study of the Liver (EASL), the Association of European Cancer Leagues (ECL), the European Liver Patients Association (ELPA), Pancreatic Cancer Europe (PCE), Europacolon and Eurocare (The European Alcohol Policy Alliance). Alcohol and Digestive Cancers 3 Time for Change

Europe is the region with the highest level of alcohol consumption “in the world and, as a result, Europe bears the highest burden of ill health and premature death linked directly to alcohol.

To address this endemic matter, tackling the harmful use of alcohol should be a key priority for the European Union. Appropriate response has to be comprehensive, encompassing policies and interventions from alcohol taxation, availability and marketing regulations to good access to counselling and treatment.

We welcome and support involvement and contributions from medical and research communities in the alcohol policy debate. Evidence, brought forward in reports from organisations like United European Gastroenterology help the policy makers to acknowledge the priority of addressing harm related to alcohol and deliver improved health outcomes throughout Europe.

Dr Marris Jesse ”Deputy Secretary General for Health Representative of the Estonian European Union (EU) Presidency 4 Alcohol and Digestive Cancers Time for Change

Introduction

United European Gastroenterology (UEG) is committed to raising political and public Despite attempts in Europe to tackle the awareness of digestive health conditions. “impact of alcohol on health, the amount This involves encouragement of research to of alcohol consumed by EU countries is higher reduce the incidence and mortality rates of than the rest of the world and the incidence digestive diseases, informing policy makers of many alcohol related digestive cancers to help drive digestive health strategies on is on the increase. It is, therefore, time for an EU level and to improve patient outcomes a change. We urgently require a focused throughout the continent. multi-dimensional approach from policy It is commonly known that lifestyle factors have a significant and decision makers at both European and impact on digestive diseases. Alcohol consumption, in particular, national levels to dramatically increase public is a risk factor in over 60 types of diseases, with nearly 30% and healthcare professional awareness of the of deaths from gastrointestinal diseases directly attributed to alcohol.1 Currently, the European region has the highest dangers of alcohol, as well as to implement proportion of total ill health and premature death linked directly further strategies across the region to reduce to alcohol consumption in the world.2 alcohol intake and the resulting incidence Alcohol consumption is also a known risk factor in many of digestive cancers. digestive cancers, including oesophageal, liver, pancreatic, colorectal and gastric cancer. Canvassing the opinions of leading European digestive cancer Professor Michael Manns specialists, stakeholder organisations and patient groups, ”UEG President 2015-2017 this review highlights the scale of alcohol consumption across Europe, its direct and indirect impact on digestive cancers and the alarming lack of awareness of the link between alcohol and digestive cancers among members of the public and many healthcare professionals. Alcohol and Digestive Cancers 5 Time for Change

Recorded alcohol consumption per capita3

AMERICAS

EUROPE

WESTERN PACIFIC

SOUTH EAST ASIA

EASTERN MEDITERRANEAN

AFRICA

0 1 2 3 4 5 6 7 8 9 10

LITRES OF PURE ALCOHOL 6 Alcohol and Digestive Cancers Time for Change

Alcohol & Digestive Cancers

The link between alcohol and cancer has been well documented Over one fifth of the since the early 20th century. In “European population aged particular, alcohol has been shown 15 years and above are to cause cancer of the mouth, drinking heavily at least pharynx, larynx, oesophagus, liver once a week. This approach and colon.4 9 in 10 people are to alcohol consumption, the unaware that The European Prospective Investigation into lack of awareness and the alcohol increases Cancer (EPIC Study), which assessed the complacency regarding the the risk of impact of the amount, frequency and type of associated increased risk of 7 alcohol consumed, found that alcohol was cancer responsible for about 57,600 cases of cancer digestive cancers, needs to of the upper digestive tract, colon and liver in be addressed urgently. men and 21,500 cases in women. For men, 57% of these cases related to those who regularly drank more than two alcoholic drinks Professor Stephan Haas a day, while for women, a staggering 80% Center for Digestive Diseases, Karolinska of cases related to those who regularly drank ”University Hospital, Sweden more than just one alcoholic drink a day.5 However, according to the European Alcohol Policy Alliance, Eurocare, millions of Europeans remain unaware of the risks of alcohol consumption, with 1 in 5 revealing One fifth of the that they do not believe there is a connection European population between alcohol and cancer.6 In addition, aged 15 and above a recent Cancer Research UK study showed as many as 9 in 10 people are unaware that are drinking heavily alcohol increases the risk of cancer.7 at least once a week 2 Alcohol and Digestive Cancers 7 Time for Change

Alcohol and European culture The science behind the European Code “against Cancer leaves us in no doubt that From the earliest recorded consumption of consuming alcohol can cause at least 7 types alcohol, drinking has been regarded as a social of cancer. For this reason, the European and celebratory activity. Therefore, the main Code advises people to limit their alcohol challenge preventing successful actions aimed intake or, better still for reducing your cancer at addressing drinking levels across Europe is risk, avoid drinking alcohol altogether. how deeply embedded alcohol consumption Unfortunately, the link between alcohol is within European society, both socially and consumption and cancer is not widely known culturally. and understood. Given the well-established science on this issue, it’s imperative that policymakers support actions that will bring Alcohol consumption in these spirits may have a high into clearer focus for citizens the increased Europe decreased in the methanol content which can cancer risk from drinking alcohol. 1990’s, but has increased be very toxic.” again in the last decade to stabilise at more than Evidence shows a direct Dr. Wendy Yared an average of 9 litres of correlation between drinking Director, Association of European Cancer Leagues (ECL) pure alcohol per year per culture and higher cancer ” 8 risk, with heavy episodic capita. There is, however, considerable cross-cultural drinking being associated variation among European with a higher incidence countries regarding alcohol of digestive cancers.9 consumption and this has an For example, the higher impact on cancer incidence incidence of colorectal rates. Professor Haas cancer in eastern Europe, explains; “Unfortunately, the compared to France and drinking pattern in some Italy, is thought to be as a The risk of dying from an eastern EU countries favours result of heavy spirit drinking alcohol-attributable cause is high alcohol intake, such as after work as opposed to vodka and schnapps and, the Mediterranean habit 7 times higher in the Eastern due to the unsophisticated of consuming a moderate European Region than the distillation processes in amount of wine as an Mediterranean Region 2 many of these countries, accompaniment to a meal. 8 Alcohol and Digestive Cancers Time for Change

Total alcohol per capita (≥ 15 years of age) consumption, projected estimates, 201610

MALTA ITALY GREECE NETHERLANDS SWEDEN SPAIN CYPRUS DENMARK AUSTRIA PORTUGAL FINLAND IRELAND LUXEMBOURG SLOVENIA GERMANY FRANCE UNITED KINGDOM LATVIA POLAND HUNGARY SLOVAKIA ESTONIA BELGIUM CROATIA BULGARIA ROMANIA CZECH REPUBLIC LITHUANIA

0 2 4 6 8 10 12 14 16 18 20

LITRES OF PURE ALCOHOL Alcohol and Digestive Cancers 9 Time for Change

Alcohol Type

Research into which type of alcoholic beverage has the most significant role in cancer risk remains inconclusive.

Although most studies do not report any explains; “One challenge is the school variation in the risk of digestive cancers of thought that moderate alcohol The risk of cancer incidence being increased by a particular type of consumption, particularly red wine, “rises exponentially with alcohol,11 it appears that the greatest is often considered to be healthy. risk derives from wine and to a lesser According to animal experiments, there the amount of alcohol degree from beer and spirits.12 This is is some truth to this. However, many consumed. Drinking 3 likely to be as a result of consuming regular drinkers have a certain level times the recommended large quantities of cheap wine which of addiction and there is then a very can also contain other harmful different and more serious risk profile.” amount increases the ingredients. This has been evident risk of oesophageal with the recent dramatic reductions There is considerable debate about whether alcohol with higher cancer by 8 times. There in liver disease and deaths as a result of a reduction in cheap table wine concentrated forms of ethanol, such as is currently no known or consumption in Mediterranean wine- spirits, has a greater impact on the risk established level of safe drinking countries.13 of digestive cancer. This is exacerbated by the fact that ethanol content can alcohol consumption when However, this evidence is often differ according to the type of drink relating to cancer risk. contradicted by messaging that suggest and may vary by country, with ethanol that drinking red wine has positive content in beer ranging from 2.3% to health benefits, when in fact any level over 10%, wine from 8% to 15%, spirits Professor Stephan Haas of alcohol consumption increases the from 20% to over 40% and as high as Digestive Cancer Expert, Karolinska risk of cancer. Professor Matthias Löhr 80% for some kinds of absinthe.14 ”University Hospital, Sweden 10 Alcohol and Digestive Cancers Time for Change

How much is too much? Number of drinks per day Light The most recent meta-analysis study Up to or 1 drink per day (≤1) assessing dose-response alcohol consumption and site specific cancer Moderate More than 1 and up to 4 drinks per day (>1 and <4) risk reveals, regardless of the type of beverage, even light drinking of up to Heavy 1 alcoholic drink a day carries an 4 or more drinks per day (≥4) increased risk of oesophageal cancer, consuming between 1-4 alcoholic drinks a day increases the risk of colorectal cancer and 4 or more alcoholic drinks a day is linked to an increased risk of liver, gastric and pancreatic cancer.15 1 alcoholic drink a day increases the As Professor Bohumil Seifert explains; risk of oesophageal “Three quarters of oesophageal cancer is linked cancer to alcohol misuse and mouth, throat, oesophageal, pancreatic and small bowel cancers are all increasing in incidence. It’s fair to say that this is, in part, due to alcohol consumption.” between 1-4 Members of the public are provided with mixed messages about recommended units, volumes alcoholic drinks and glasses of alcohol and this does not help a day increases the in the public or healthcare professional assessment risk of colorectal of health risk. cancer Recent meta-analyses do not suggest a significant impact of drinking patterns on risk of total cancer in light to moderate drinkers.16 Four or more drinks a day, however, has been linked to a significantly increased 4 or more alcoholic risk of digestive cancers and the risk of colorectal cancer drinks a day is also increased by 21% when having between 1-4 increases the risk of alcoholic drinks per day.15 gastric, pancreatic and liver cancer Alcohol and Digestive Cancers 11 Time for Change

How does alcohol cause digestive cancer? The combination of Extensive research has identified multiple ways that alcohol may “cheap alcohol with a increase the risk of digestive cancers both by damaging cells, as well higher concentration as a result of the metabolising of ethanol, the intoxicating ingredient of ethanol in drinks in alcoholic beverages. like beer, schnapps or vodka, coupled with smoking, is the Ethanol is widely recognised as the There is also a significant body of research agent predominantly accounting for and it is commonly accepted that there is fundamental reason carcinogenesis17 and recently the a genetic predisposition for people to drink, for the high incidence International Agency for Cancer Research and epigenetics, changes in gene expression of digestive cancers (IARC) concluded that acetaldehyde, and activity, can be inherited and can affect the by-product created when metabolising the risk of disease. particularly in eastern 12 alcohol, is carcinogenic to humans. Many heavy drinkers are also smokers which Europe. Specifically, according to a review of current further increases their risk of digestive cancer. evidence demonstrating the causal effect It is thought that alcohol facilitates access of alcohol on digestive cancers, functional for tobacco carcinogens to also penetrate Professor Matthias Löhr genetic variants of alcohol-metabolising the mucosa in the upper digestive tract,19 UEG and Pancreatic Cancer enzymes proved to be associated with making the risks associated with using both ”Europe cancer expert increased risk for oesophageal and gastric alcohol and tobacco greater than would be cancer. The highest risk increase for expected from adding together the individual malignancy was observed in the upper risks associated with alcohol and tobacco.20 aerodigestive tract (oral cavity, pharynx, Research shows that smoking not only larynx) and oesophagus, with weaker changes the oral bacterial flora but also correlations established for gastric, increases the level of salivary acetaldehyde.21 pancreatic and colorectal malignancies.18 Alcohol may increase the risk of cancer by The mechanisms by which alcohol causes generating chemically reactive molecules cancer are also thought to depend upon that contain oxygen which can damage DNA, the particular organ. Most ethanol will be proteins and lipids. It is generally regarded metabolised to acetaldehyde in the liver but that too much alcohol can impair the body’s salivary acetaldehyde has also been found ability to break down and absorb cancer to reach high levels while drinking. There protecting nutrients such as vitamins, folate is considerable evidence that DNA damage and carotenoids.22 Dietary deficiencies such as and resulting cancer in the oesophagus a lack of folate, riboflavin, and zinc may also (as well as of the mouth, larynx and contribute to the increased cancer risk in an pharynx) is due to acetaldehyde.19 alcoholic patient.21 12 Alcohol and Digestive Cancers Time for Change

Alcohol and Oesophageal Cancer

Incidence Evidence Oesophageal cancer is one of the most Alcohol misuse is only known to be a clear risk factor for one type of common digestive cancers linked to alcohol oesophageal cancer, oesophageal squamous-cell carcinoma (ESCC), which consumption. When examining the burden occurs at the upper end of the oesophagus. As Professor Rebecca Fitzgerald of cancer attributable to former and current explains: “Alcohol is associated with a number of cancers in the upper alcohol consumption, the EPIC study found digestive tract, typically oral, pharynx, larynx and squamous cell cancer of that incidence was 44% of cancers of the the oesophagus but, at the moment, we don’t have sufficient evidence to upper aerodigestive tract in men and 25% determine if certain types of alcohol or particular drinking patterns increase for women.23 In fact, oesophageal cancer the risk of ESCC more than others.” contributes to nearly a third (27%) of alcohol- attributable cancer deaths in men.17 The highest incidence of ESCC and drinking at work regulations Oesophageal cancer is one of the deadliest in Europe is in north eastern in France, helping to reduce cancers worldwide because of its extremely European countries and the lowest alcohol consumption, particularly aggressive nature and poor survival rate. in Scandinavia and it typically in younger men. Smoking has also The annual incidence of oesophageal cancer affects people aged between 60 declined in both countries due to in the UK, for example, is 9.6 out of 100 000 and 80 years old.26 Typically, ESCC banning smoking in public places, population. With a five-year survival rate is more common in women and which has also had a positive of under 10%, the annual mortality rate of in some parts of France ESCC is impact on reducing ESCC incidence. oesophageal cancer is almost as high as the particularly high and this has been The genotype of the consumer also incidence rate, at 8.7 out of 100 000 people.24 linked to drinking hot Calvados. increases the risk of oesophageal In spite of the relatively high cancer, with those carrying the incidence of ESCC in France and ALDH2 gene experiencing a the UK, rates have been declining higher risk of oesophageal cancer recently and this is thought to be for the same amount of alcohol due to stricter alcohol advertising consumed.17 oesophageal cancer is the sixth largest cancer killer worldwide 25 Alcohol and Digestive Cancers 13 Time for Change

What needs to change? People are used to A change in attitude towards alcohol is key to reducing consumption, as Professor “smoke-free zones now, Fitzgerald emphasises; “Further educational public awareness campaigns would be helpful so it isn’t inconceivable to reduce ESCC as a result of alcohol consumption, but there needs to be cultural changes too. In eastern Europe, drinking excessively, particularly amongst men, is an intrinsic part that the same of their culture and this needs to change. As the French have shown, reducing their alcohol could happen with consumption has helped reduce the incidence of oesophageal cancer.” alcohol, thereby reducing accessibility, As well as improving public awareness Future hopes to facilitate earlier diagnosis of the link between alcohol and ESCC, may rest on a current primary care trial consumption levels it is vital, due to its poor prognosis, with 9,000 patients currently underway and digestive cancer to diagnose oesophageal cancer at an in the UK, allowing doctor’s surgeries to incidence, as a result. early stage before the development test for Barrett’s oesophagus, a condition of symptoms, when treatment can that can increase the risk of developing dramatically improve prognosis. oesophageal cancer.27 Professor Fitzgerald, who leads the study explains: “It’s a safe Professor Rebecca Fitzgerald Improved primary care identification of and relatively straightforward test. We hope Oesophageal cancer expert, high risk patients and understanding that this will make it easier for healthcare ”Addenbrooke’s Hospital, Cambridge, of the pathogenesis of ESCC is key to professionals working in primary care to London diagnosing these cancers early in order identify patients who have an increased risk to improve outcomes. “Essentially, of developing oesophageal cancer without primary care interventions need to be having to refer them to hospital. Within 3-5 improved and delays for endoscopies years we will have the evidence required reduced. The referral pathway for to see whether it is possible to introduce cancer shows that not all patients are this test into primary care as a triage to seeking help and being referred in a see which patients should be referred for timely manner. Data from the UK has endoscopy.” shown that GPs with low referral rates for endoscopy correlates with patients diagnosed with oesophageal cancer at a later stage,” warns Professor Fitzgerald. 14 Alcohol and Digestive Cancers Time for Change

Alcohol and Liver Cancer

Incidence Evidence In the European Region, more than Alcohol consumption is an independent nearly 24% of all such deaths and also the 2,370,000 healthy life years are lost risk for, and primary cause of, liver cancer29 largest contributor to disability-adjusted from liver disease before the age of 50; with more than half of all primary liver life years lost.17 However, it is also possible more than lung, trachea, bronchus, cancer cases caused by cirrhosis brought that alcohol consumption is systematically oesophageal, gastric, colorectal and on by harmful consumption of alcohol. under-reported in several studies, resulting 29 in an under-estimation of the real extent of pancreatic cancer combined. Alcohol abuse accounts for 40-50% of all the impact of alcohol on liver cancer.32 Any health condition that causes cirrhosis liver cancer cases in Europe30 and a recent (scarring) of the liver can lead to liver meta-analysis of 19 studies showed that cancer but certain causes of cirrhosis have consumption of three or more drinks per a particularly strong link with liver cancer, day resulted in a 16% increased risk of liver The increasing levels of liver cancer, while consumption of six or more which is the fifth most common cause of “related deaths that we’ve seen cancer in Europe, responsible for around drinks per day resulted in a 22% increased 31 47,000 deaths per year.8 risk. in the UK and Finland are very The occurrence of liver cancer is also likely to be due to changes in more prevalent in men than women drinking patterns. and according to the recent EPIC Study, the incidence of liver cancer found to be With viral hepatitis in sharp attributable to alcohol consumption was Professor Helena Cortez-Pinto “decline in Europe, alcohol will 33% for men and 18% for women.23 EU Policy Councillor for the European take the number 1 position ”Association for the Study of the Liver (EASL) Trends in alcohol consumption correlate as cause of liver cancer with closely with trends in overall mortality caused by liver disease. There is increasing incidence in Eastern considerable disparity across the EU Europe and Great Britain. regarding liver deaths, with France and Political action is needed to Italy having a three-to fourfold reduction in liver mortality, whereas the UK and Finland stop these trends. have seen liver deaths rise by more than fivefold over the same period of time.30 alcohol abuse accounts Professor Markus Peck In 2010, the largest contributor to the Liver cancer expert and Chair-elect of UEG burden of alcohol-attributable cancer for up to half of all liver 30 ”Public Affairs Committee deaths was liver cancer, responsible for cancer cases in Europe Alcohol and Digestive Cancers 15 Time for Change

It is thought that the link between What needs to change? alcohol and liver cancer is as a result of the carcinogenicity of acetaldehyde Alcohol has many health Another important strategy is raising as well as several other biologic “risks and excessive drinking awareness of the risk of alcohol via mechanisms. These include chronic labelling of alcoholic beverages. inflammation, which leads to increased causes damage to many Informative labelling should be oxidative stress, DNA damage and areas of the body, especially provided for members of the public decreased hepatic retinoic acid, as well the liver. The more people to ensure that they are able to make as impairment of the immune system, truly informed, as well as healthy, which can lead to further complications cut down their levels of decisions. Ireland has implemented and infections.32 alcohol consumption, the stricter labelling requirements on “There is no evidence that the type of more they cut their risk certain alcoholic beverages and it is alcohol makes a difference, since it hoped more European countries will of cancer. It is therefore follow suit. depends on how alcohol is metabolised vital that the European and this is not affected by the type As Professor Cortez-Pinto emphasises, of alcoholic beverage. It is also the population are fully aware “There is strong evidence of many total amount consumed in a week of the dangers of drinking public health policies that have reduced that is important. It doesn’t matter alcohol to help reduce overall the levels of alcohol consumption which whether it is all consumed in a day or has had a direct link to a reduction gradually across the week but overall consumption which, in turn, in deaths. In general, all policies that high levels of consumption do have could decrease the incidence increase the price of alcohol, reduce an impact on increasing the risk of of liver cirrhosis and liver availability, improve the publicity on the liver cancer,” Professor Cortez-Pinto risks and increase the minimum age to explains. “Once liver cancer has been cancer. buy alcohol have led to an immediate diagnosed, stopping alcohol has been reduction in the incidence of alcohol- demonstrated to have a favourable related liver disease and deaths. effect on the progression of cirrhosis.” Tatjana Reic Continuing to implement these policies President, European Liver Patients’ across Europe to tackle high and rising Liver cancer caused by harmful alcohol ”Association consumption can take many years to levels of drinking is essential if we’re develop and it is likely that the liver going to reduce the number of people cancer rates linked to alcohol have not with liver cancer in the future.” yet peaked and are forecast to continue to rise.33 16 Alcohol and Digestive Cancers Time for Change

Alcohol and Pancreatic Cancer

Incidence Evidence Pancreatic cancer survival rates Whilst further research is required, there is accumulating evidence that drinking alcohol have remained alarmingly low is associated with pancreatic cancer in heavy drinkers (four or more drinks a day), with binge at just 3-6% for more than 40 drinkers (over 5 drinks a day) reported to have a significantly higher risk.37 years.34 Deaths are predicted to The increased risk for heavy drinking is similar in women and men.38 surpass those of breast cancer in the EU in 2017, making it the third biggest cancer killer in According to Professor Stephan Haas; in hand to exacerbate damage to cancer- Europe.35 “There is a direct link between alcohol associated pancreas cells, triggering misuse and the increased incidence of carcinogens which may then proliferate pancreatic cancer. However, this link has abnormally to form cancer. There is also proved to be inconsistent as epidemiological a very strong link between certain bacteria studies face some significant methodological and pancreatic cancer and this, combined problems. For example, it is difficult for with alcohol, smoking and poor diet, has patients to recall the precise amount a synergistic effect, further increasing the when asked about their consumption risk of pancreatic cancer.” during their life and people also tend to Studies have shown that in those patients under-estimate. Research in this field is with a genetic predisposition to pancreatic Third biggest even more difficult, as different researchers cancer, use of tobacco and alcohol has been cancer killer use different definitions of an alcoholic drink. associated with an earlier age of diagnosis 35 It is therefore challenging to obtain correct in Europe for the disease.39 Furthermore, researchers information when recording drinking found that smokers and drinkers, especially patterns.” heavy drinkers, experience onset of the What is not in doubt is the inextricable link disease at an earlier age than non-smokers between alcohol and other lifestyle factors and non-drinkers. However, patients who had in the increased risk of pancreatic cancer. stopped smoking or consuming alcohol for “There is a small incremental increase in more than 10 years had the same age at onset the risk of developing pancreatic cancer if of their cancer as lifetime non-smokers and The median survival time you only drink alcohol but a huge increased non-drinkers. Although beer drinkers develop following a pancreatic risk if you smoke as well” explains Professor pancreatic cancer at an earlier age than non- cancer diagnosis is 4.6 Matthias Löhr. “Heavy drinkers are often drinkers, alcohol type did not have months36 smoke too and both risk factors go hand a significant effect.39 Alcohol and Digestive Cancers 17 Time for Change

The biological mechanisms accounting for how alcohol What needs to change? intake may cause pancreatic cancer are unclear and require further research. However, potential mechanisms As pancreatic cancer survival is consistently low, with an average include pancreatitis and the accumulation of fatty acids in survival rate of less than 18 months, it is vital that risk profiling, the pancreas, which may induce inflammatory responses diagnosis and treatments are improved, as well as a greater and fibrosis.17 Acute pancreatitis also provides patients understanding of the causes of the disease to facilitate prevention. with a higher risk of pancreatic cancer and alcohol is the most common cause of pancreatitis identified in eastern, nothern and western Europe.40 “However, it is clear also that pancreatitis is not necessarily a UEG and Pancreatic Cancer Europe undertake precursor for pancreatic cancer and according to our “important work in raising awareness of the causes, current knowledge, alcohol can induce pancreatic cancer even when the patient has not developed a chronic risk factors and symptoms of pancreatic cancer but pancreatitis”, adds Professor Stephan Haas. the public and medical profession still need to be more aware and simply ‘think’ about pancreatic cancer when faced with certain symptoms to ensure the earliest possible diagnosis.

Professor Matthias Löhr ”UEG and Pancreatic Cancer Europe cancer expert Currently, there are no generally accepted screening tests for The combination of alcohol and pancreatic cancer and screening is not recommended for the general “smoking is the fundamental reason population. Screening for patients with a family history of pancreatic cancer using endoscopic ultrasound has had limited success but for eastern Europe’s high incidence the optimum age at which to initiate screening is unclear.39 As a of digestive cancers. result, there remains an urgent need amongst the pancreatic cancer healthcare community to clarify screening requirements as well as for international collaborations to drive new research and increase public Professor Matthias Löhr awareness of the disease to improve survival rates. ”UEG and Pancreatic Cancer Europe cancer expert 18 Alcohol and Digestive Cancers Time for Change

Alcohol and Colorectal Cancer

Incidence Evidence Colorectal cancer (CRC) is the In 2007, International Agency for Research is increased in patients who drink, but it second most common cancer on Cancer (IARC) added CRC to the list of is often difficult to estimate the direct risk in Europe, accounting for 13% cancers causally related to alcohol.43 Unlike factors clearly as most people are likely to of all cancers and is the most most other digestive cancers associated have other potential causative factors, such common digestive cancer, with alcohol, meta-analysis examining the as a poor diet, with low dietary folate or accounting for about half of all association between alcohol consumption tobacco use. As the incidence of colorectal digestive cancers in Europe.41 and CRC risk shows there is an increased risk cancer is increasing in younger people, and The incidence of CRC is higher of 21% in those who consume between 1-4 this does not seem to be explained by clear in men than women. Mortality alcoholic drinks per day and as much as a genetic cancer syndromes, it follows that is on the increase in many 52% increased risk in those who consume lifestyle factors, including alcohol misuse, eastern European countries as more than 4 drinks per day.44 might add to the risk of colorectal cancer well as some parts of southern in these young patients,” she adds. 26 It is still uncertain whether the effect of Europe and the global burden alcohol varies across the colon and rectum. As with other digestive cancers, studies of CRC is expected to increase Some studies have reported a stronger show there is no clear difference in relative by 60% to more than 2.2 million alcohol-cancer risk association in the colon risk for different types of alcohol on CRC. new cases and 1.1 million that in the rectum, whereas others have As Professor Dekker points out; “the type of 42 deaths by 2030. found a stronger, or similar, association for alcohol and direct effect of ethanol is more the rectum. The dose-response relationship likely to influence upper GI cancer risk and is also less apparent in women, possibly have more of an indirect effect on lower as they tend to consume less alcohol than gastrointestinal cancers, via the metabolising men, but findings have shown a small of alcohol in the liver and production of the increased risk for rectal, but not colon cancer, carcinogenic enzyme acetaldehyde.” in women.44 The EPIC Study found that the incidence of CRC amongst former and current alcohol consumers was 17% for men and 4% for women.23 “Exactly how alcohol increases the risk of Second most CRC is not well understood and needs more research,” highlights Professor Evelien common cancer Dekker, UEG CRC expert. “There is certainly increased risk of CRC with just in Europe 41 the suggestion that colorectal cancer risk 1 alcoholic drink per day44 Alcohol and Digestive Cancers 19 Time for Change

What needs to change? We know a lot about the risks Awareness programmes recommending limiting alcohol intake, even by up to “that can cause colorectal cancer 2 drinks a day, are vital to dramatically reduce the risk. According to Professor Dekker; “The most vital requirements to reduce alcohol induced colorectal but changing behaviour is always cancer and reduce mortality rates are to urge people not to be a moderate challenging. The first step for or heavy drinker. More risk-based screening programmes are needed, not just breaking a bad habit is recognising a one size fits all approach, but to accommodate younger ages as well as those at higher risk, including heavy drinkers and smokers. For those with an and taking personal responsibility increased risk, a lower faecal test result might also justify being called in for for our health. Alcohol can be a colonoscopy.” very addictive but knowing Currently, the UK is setting the standard for best practice referral pathway with alcohol safety levels is imperative. a unique 2-week referral programme, ensuring the earliest possible diagnosis. EuropaColon campaigns for “There is better availability of special services for patients with alarm symptoms in many countries but this can still be improved. Not all European countries education for better public health implement colorectal cancer screening programmes at a national level and awareness. recruitment is always difficult,” Professor Bohumil Seifert explains. Professor Dekker highlights; “there are still many barriers to the early detection of colorectal cancer that urgently need to be overcome, such as compliance, the Jolanta Gore Booth type of test, age of screening and invitation methods and there is still a long way CEO and Founder, EuropaColon “ to go for all countries to improve uptake rates.” The question that remains for policy makers is whether screening programmes should be provided for those with an increased risk due to lifestyle factors including, heavy drinking, poor diet and smoking.

increased risk of CRC with more than 4 drinks per day44 20 Alcohol and Digestive Cancers Time for Change

Alcohol and Gastric Cancer

Incidence Gastric, or stomach cancer, is the fifth most common cancer in the world.45 Alcohol has a large part Europe and Asia have the highest incidence45 of gastric cancer with more than “to play in causing gastric 46 139,000 new cases estimated to have been diagnosed in Europe in 2012. cancer, not just as a result of the carcinogenic effect Evidence of acetaldehyde but also Gastric cancer is more common in Research Fund,48 approximately one because as it is metabolised, older adults and is about twice as in seven gastric cancer cases could the body does not metabolise common in men than women.45 be prevented if people did not drink Chronic heavy drinking, particularly more than three alcoholic drinks a other fats and sugars when accompanied by the abuse day, did not eat processed meat and efficiently, slowing down the of tobacco, is associated with an maintained a healthy weight. metabolism and ultimately increased risk of gastric cancers.15 Unlike most other digestive cancers, In fact, according to the meta- leading to weight gain and researchers found that beer analysis examining the effect on increases the risk of gastric cancer.47 a further increased risk of alcohol and digestive cancers, heavy developing cancer. drinking causes causes the same increased risk of gastric cancer as What needs to change? colorectal cancer.15 It is clear that European public Professor Stephan Haas Digestive Cancer Expert, Karolinska A study of more than 500,000 adults, awareness campaigns to highlight also suggests that heavy-drinking ”University Hospital, Sweden the conclusive evidence of the link men, averaging four or more drinks between heavy drinking, smoking per day, were twice as likely to and obesity and an increase in develop gastric cancer over the next gastric cancer are essential to decade as those of light drinkers dramatically reduce the incidence who had the equivalent of about half of gastric cancer across Europe. a drink per day or less.47 According to a recent report by the American Institute for Cancer Heavy drinkers twice as Research and the World Cancer likely to develop gastric cancer than light drinkers Alcohol and Digestive Cancers 21 Time for Change

Evidence states that light, “moderate and heavy alcohol consumption all increase our risk of digestive cancers. It is imperative that Oesophageal cancer Heavy immediate action is contributes to nearly drinking undertaken, by both a third of alcohol- causes a 21% attributable increased risk healthcare professionals cancer deaths in men 17 of gastric and policy makers, cancer 47 to increase public awareness of this risk and allow consumers to make more informed choices about their Alcohol abuse accounts drinking habits. for up to half of all liver cancer cases in Europe 30 Five or more Professor Thierry Ponchon Chair of the UEG Public Affairs drinks per ”Committee drinking episode results in a 3.5 increased 21% increased risk of CRC risk of with the consumption of one pancreatic alcoholic drink per day 47 cancer 37 22 Alcohol and Digestive Cancers Time for Change

Alcohol and Digestive Cancers: Complacency about, and social Implications for the Public “acceptance of, drinking alcohol in Europe is deep-rooted and difficult to change. The younger generation The World Cancer Report, produced by the World Health seem more aware of the dangers Organisation’s specialised cancer agency, predicts new and are stricter about avoiding cancer cases will rise from an estimated 14 million annually alcohol but the middle and older in 2012 to 22 million within two decades. Over the same generations are very difficult to period, cancer deaths are predicted to rise from 8.2 million influence. a year to 13 million. The report also highlights that about half of all cancers are preventable and the disease could be tackled by addressing lifestyle factors, such as alcohol Professor Bohumil Seifert European Primary Care Expert consumption as well as smoking, diet and exercise and the ” widespread implementation of screening programmes.49

There is strong evidence to suggest A person’s risk of alcohol-related that the more alcohol people drink, cancers is also largely influenced the higher the risk of digestive by their genes, specifically We need patients to be more aware cancer but as Professor Bohumil the genes that are involved in “of their risk profile, due to both Seifert explains; “Awareness about metabolising alcohol. There is the dangers of drinking across considerable evidence highlighting their genetic and lifestyle factors Europe is poor and a population- the genetic predisposition to and to seek help as soon as they wide pan European educational drinking.50 Educating younger campaign to highlight the link generations about the genetic risk experience symptoms, to take between alcohol misuse and of alcohol dependence is likely to advantage of early treatment and digestive cancers is essential to also increase awareness of their ensure better prognosis. inform the public about how susceptibility to drink which may drinking impacts their health and help them to seek advice earlier the simple steps they can take to and reduce the likelihood of Professor Matthias Löhr significantly reduce their risk.” alcohol misuse. ”UEG and Pancreatic Cancer Europe cancer expert Alcohol and Digestive Cancers 23 Time for Change

There needs to be a seismic shift in attitudes towards social drinking to address the complacency concerning the negative effects of alcohol, as well as dramatically changing the general lack of awareness about the impact of even moderate regular drinking on digestive cancers. Change in The alcohol industry has an important part to play in responsible labelling of alcohol, public attitude as Professor Haas explains; “Many beverages contain harmful ingredients as well as pure towards alcohol ethanol and the industry should provide mandatory health information detailing all the ingredients, amount of alcohol and calories on every bottle or can, to ensure the public consumption is are fully informed about what they are drinking.” urgently required Patients’ awareness of symptoms is essential to prompt early referral and diagnosis and although much has been done to highlight alarm symptoms for many digestive cancers, not seeking advice or seeing the family doctor due to embarrassment or complacency is still a serious concern and barrier to early diagnosis. Patients can also overlook the severity of their symptoms as they may ‘come and go’ leading them to believe they aren’t serious.

Five million rise in cancer deaths by 203051

In France, changes to regulations and cultural eating habits with “people no longer permitted to drink wine at work, as well as enforcing stricter alcohol advertising regulations, has reduced alcohol consumption with digestive cancer incidence declining as a result.

8 million rise in new Professor Fitzgerald 51 cancer cases by 2030 ”Oesophageal cancer expert, Addenbrooke’s Hospital, Cambridge, London 24 Alcohol and Digestive Cancers Time for Change

Alcohol and Digestive Cancers: Identifying at risk patients is key to Implications for Primary Care early diagnosis Practitioners Education campaigns are vital to mobilise patients to seek advice and treatment but also for primary care As mortality rates for many digestive cancers are too high, practitioners to identify at risk patients and to recognise prevention of digestive cancers is vital to stop incidence rates alarm symptoms as early as possible. Risk assessment from rising. The family doctor is best placed as the first-line and intervention techniques differ widely across contact with patients to detect alcohol misuse, implement Europe and need to be improved within primary care intervention programmes and also to assess alarm symptoms as consultations to facilitate more effective referral for early as possible, ensuring the quickest diagnosis and treatment. screening and to maximise patient outcomes. As the EPIC study has shown, the impact of alcohol on digestive Concentrating on risk assessment in the Czech Republic, cancers is not just as a result of heavy drinking well above Professor Seifert explains; “We always undertake the recommended amounts. Primary care practitioners are a questionnaire when accepting patients into the best placed to identify at risk drinkers and either recommend practice and ask general questions about the amount abstinence for high risk drinkers or to reduce intake to one of alcohol they consume. However, this audit test is not or less drinks per day, in order to significantly reduce their very effective as you cannot be sure that the patient is patient’s risk of digestive cancers associated with alcohol. In accurately reporting their consumption. As a result, we fact, recommendations to cut back from 4 or more drinks per now use a more detailed, sophisticated questionnaire day to one or less drinks per day, potentially reduce a person’s which is a better way to identify a high-risk drinker. risk of colorectal cancer by over 20%.44 Rather than the usual ‘do you drink’ questions, it helps to assess whether the patient is able to abstain and how often they drink. This type of test should be rolled out more widely to identify at-risk drinkers. In the same way as smokers are referred, risk drinkers follow a ‘brief There is little awareness amongst primary intervention’ pathway where the risks of drinking and “care practitioners about the consequences of the link to digestive cancers are explained in detail.” drinking alcohol and increased digestive cancer Professor Seifert recognises, however, “It is very difficult to ‘treat’ heavy drinkers as although you can refer risk. It is vital to highlight this link and the them to a special unit for alcohol dependency, they significant digestive cancer risk associated with can only go on a voluntary basis.” Patient awareness moderate drinking as well as heavy drinking of the link between alcohol and digestive cancers as well as symptom awareness are likely to be the main in order to reduce the incidence. behavioural drivers for patients to seek treatment.

Professor Bohumil Seifert ”European Primary Care Expert Alcohol and Digestive Cancers 25 Time for Change

Access to diagnostic services and Screening key to reducing mortality “specialists needs to improve across Quick referrals and improved screening programmes are Europe as there is still considerable essential to maximise patient outcomes. The UK and Czech Republic currently have some of the most successful treatment disparity between countries. There needs pathways and programmes, as Professor Seifert highlights: to be European recommendations to “In the Czech Republic the incidence of colorectal cancer help improve primary care awareness was amongst the highest in Europe but it is now down to 7th place and mortality is decreasing which could well be due of the dangers of alcohol and its link to improved screening programmes. The public and family to digestive cancers and the importance doctors in the Czech Republic are now more aware of the alarm of early diganosis. symptoms so primary care practitioners refer earlier, ensuring quicker diagnosis and improved patient outcomes.” Novel point of care screening techniques in doctors’ practices, Professor Bohumil Seifert such as the Cytosponge test and microbiota profiling could ”European Primary Care Expert provide even earlier diagnosis for patients and are exciting screening techniques that could be implemented within the next few years. New research investigating the consequences of alcoholism on human gut microbiota, found that the gut microbiota of alcoholics was depleted in short-chain fatty acids (SCFAs), produced by certain bacteria, which are known to protect against the development of CRC as a result of the impact of ethanol. As a future prevention tool, microbiota profiling to determine whether a person’s gut is lacking cancer-protecting SCFAs could more effectively verify not only if a person is an alcoholic, rather than relying on inaccurate recall, but also the likelihood of digestive cancer developing.52 Evidence from the UK screening programme also shows that other interventions, such as a GP endorsement letter, telephone advice and an enhanced patient leaflet, have increased the uptake of bowel cancer screening and such approaches could be used to engage with at-risk alcohol-dependent patients.53 26 Alcohol and Digestive Cancers Time for Change

Alcohol and Digestive Cancers: Implications for Policy Makers

Alcohol use disorders are common in Many countries have started to alcohol less accessible. There is strong developed countries, particularly where implement at a national level some evidence that policies that increase the alcohol is cheap, readily available of the policy options from the WHO’s price of alcohol, reduce availability and and heavily promoted.54 With 135,000 global strategy to reduce the harmful improve publicity of the risks associated alcohol-related cancer deaths predicted use of alcohol, addressing the with alcohol as well as increase the by 203555 and even moderate drinking availability and marketing of alcohol minimum age to buy alcohol have led to having a significant impact on increasing as well as introducing new higher an immediate reduction in the incidence the risk of digestive cancers, it is more pricing of alcohol products to reduce its of alcohol-related liver disease and vital than ever for government action accessibility. Other policy options include deaths. I, and my colleagues at EASL, and intervention to reduce the harmful reducing the public health impact of are concerned, however, that politicians use of alcohol. illicit alcohol and informally produced and the alcohol industry are reluctant alcohol, a particular priority for Eastern to implement these measures due to Professor Haas emphasises; “We need European countries. commercial interest and, as a result, we a multidimensional approach, with will not see the socio-economic as well coordinated efforts in Europe and A recent report revealed the impact of as significant health benefits,” she adds. internationally, to tackle this urgent introducing a minimum unit price for problem. The alcohol industry and non- alcohol in England. It found that over Scandinavian countries provide a government organisations need to work 20 years, a 50p minimum price per successful example of how lower together to implement proven strategies unit of alcohol could reduce deaths accessibility to alcohol, with state- to reduce alcohol consumption more linked to alcohol by around 7,200, owned alcohol selling monopolies widely.” including around 670 cancer deaths. that do not sell alcohol in the evening, It would also reduce healthcare costs reduces harmful drinking. “Accessibility The WHO’s efforts to establish a Global by £1.3 billion.56 Professor Cortez-Pinto has a direct effect on misuse and in Strategy to reduce the harmful use explains; “Defining a minimum price Germany and the UK there is access of alcohol and the European Union’s unit has proven to be extremely effective 24 hours a day, providing greater adoption of an EU Alcohol Strategy in Canada and is being implemented opportunity for alcohol misuse, will look to drive the development of in Scotland and Ireland too. Hopefully particularly for high risk drinkers, “incentive measures”. These are aimed the rest of Europe will follow shortly. with serious health risks as a result. at protecting public health against the To reduce alcohol consumption and It is important that the alcohol industry harmful use of alcohol and provide a cancers associated with alcohol misuse, take considerable responsibility for stronger impetus for EU action on the it is vital that politicians and the alcohol the increase in alcohol misuse across abuse of alcohol. industry implement measures to make Europe, particularly as the majority Alcohol and Digestive Cancers 27 Time for Change

of alcohol sales are to people who of quality wine, which is hoped to drink at hazardous or harmful levels; continue to have a positive impact. With reasonable evidence for example, in the UK around Another important strategy includes three-quarters of alcohol sales are to “at hand, political action raising awareness of the risk of alcohol hazardous or harmful consumers”57 via labelling of alcoholic beverages. like minimum pricing and Professor Haas explains. reducing access to alcohol The European Alcohol Trade Recent research collated in the associations has welcomed the EU needs to be taken now Addiction supplement, ‘Alcohol Commission’s call for a self-regulated to prevent many future marketing regulation – from research approach to alcohol labelling, aiming 79 casualties. Research has to to public policy,’ also reveals the to provide information about the overall scientific opinion that there are ingredients in alcoholic beverages to follow to generate the data positive associations between young ensure consumers are fully informed and fine-tune political action people’s exposure to alcohol marketing about what they are drinking and to in the future. and a progression to hazardous help them make healthier choices. drinking. It recommends a global Ireland has already implemented rather than European wide strategy stricter labelling requirements on and a common code for regulation certain alcoholic beverages and it is Professor Markus Peck and public health NGO’s to enforce the hoped more European countries will Liver cancer expert and Chair-elect of UEG regulations to better protect the public. follow suit. ”Public Affairs Committee Countries leading the way include More research and Europe-wide France, which has tightened agreement is also needed to resolve marketing as well as drinking the quantification for light, moderate at work regulations and seen a and heavy drinking and clearer decrease in alcohol consumption dose-response relationship studies, and digestive cancer incidence as as quantities currently differ from a result. Recent reductions in liver country to country. This will inform deaths in Mediterranean countries comprehensive public awareness alcohol-related have also corresponded to a fall in campaigns to ensure the public are the consumption of cheap table wine aware of the direct link between specific cancer deaths and the wine industry has changed quantities of alcohol consumed and the predicted by 2035 55 its model to sell smaller quantities increase in risk of digestive cancers. 28 Alcohol and Digestive Cancers Time for Change

Time for Change

There is a wealth of evidence to confirm the link between alcohol consumption and digestive cancers. However, there is much more to do to convince the public, healthcare professionals and policy makers of the urgent need for change across Europe.

United European Gastroenterology, its member organisations and stakeholder partners are collectively behind Eurocare’s recommended target for a minimum 10% reduction of total alcohol consumption by 2025 and this review highlights a number of requirements to meet this challenge. In summary, these are clear information, research, risk assessment, screening, education and marketing regulation.

Clear information Research Risk assessment Eradicate confusion and Further research to provide Improved risk assessments and mixed messaging around more data about the impact of interventions within primary alcohol consumption and different types of alcohol and care settings to increase the associated risks through clear drinking patterns on specific number of early referrals for and consistent pan-European cancer sites and how other screening and treatment information lifestyle factors and genetics affect risk Alcohol and Digestive Cancers 29 Time for Change

It is time for Europe to change its approach Policy makers at both EU and Member State level have “and attitude towards alcohol consumption. “a critical role to play in promoting cancer prevention, UEG calls upon EU policy makers and early diagnosis and the improvement of cancer citizens to recognise the evidence of the treatments. National policies targeted towards reducing digestive cancer risks associated with alcohol alcohol consumption, as well as unified screening consumption. The societal costs and healthcare programmes throughout Europe, will help to decrease implications of increased alcohol consumption the burden of digestive cancers and improve overall are huge. Now is the time to take positive and patient outcomes. The EU should look to provide pro-active action for the benefit of current and support for the Member States by setting harmonised future generations. rules and facilitating the exchange of best practice.

Professor Paul Fockens MEP Poc UEG President 2017-2019 Vice-Chair of MEPs Against Cancer (MAC), a European Parliament Interest ” ”Group

Screening Education Marketing regulation A unified approach to national Investment in public and primary Increased pressure on the screening programmes to help care education campaigns to increase alcohol industry to tighten their increase uptake rates to more awareness of the impact of alcohol marketing regulations on alcohol than 60% on digestive cancers and reduce promotion as well as more the alcohol related risk of digestive responsible labelling cancers, allowing consumers to make informed choices 30 Alcohol and Digestive Cancers Time for Change

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